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排序方式: 共有380条查询结果,搜索用时 15 毫秒
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Samuele Cortese Marco Solmi Giorgia Michelini Alessio Bellato Christina Blanner Andrea Canozzi Luis Eudave Luis C. Farhat Mikkel Højlund Ole Köhler-Forsberg Douglas Teixeira Leffa Christopher Rohde Gonzalo Salazar de Pablo Giovanni Vita Rikke Wesselhoeft Joanna Martin Sarah Baumeister Natali S. Bozhilova Christina O. Carlisi Virginia Carter Leno Dorothea L. Floris Nathalie E. Holz Eline J. Kraaijenvanger Seda Sacu Isabella Vainieri Giovanni Ostuzzi Corrado Barbui Christoph U. Correll 《World psychiatry》2023,22(1):129-149
Neurodevelopmental disorders – including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, communication disorders, intellectual disability, motor disorders, specific learning disorders, and tic disorders – manifest themselves early in development. Valid, reliable and broadly usable biomarkers supporting a timely diagnosis of these disorders would be highly relevant from a clinical and public health standpoint. We conducted the first systematic review of studies on candidate diagnostic biomarkers for these disorders in children and adolescents. We searched Medline and Embase + Embase Classic with terms relating to biomarkers until April 6, 2022, and conducted additional targeted searches for genome-wide association studies (GWAS) and neuroimaging or neurophysiological studies carried out by international consortia. We considered a candidate biomarker as promising if it was reported in at least two independent studies providing evidence of sensitivity and specificity of at least 80%. After screening 10,625 references, we retained 780 studies (374 biochemical, 203 neuroimaging, 133 neurophysiological and 65 neuropsychological studies, and five GWAS), including a total of approximately 120,000 cases and 176,000 controls. While the majority of the studies focused simply on associations, we could not find any biomarker for which there was evidence – from two or more studies from independent research groups, with results going into the same direction – of specificity and sensitivity of at least 80%. Other important metrics to assess the validity of a candidate biomarker, such as positive predictive value and negative predictive value, were infrequently reported. Limitations of the currently available studies include mostly small sample size, heterogeneous approaches and candidate biomarker targets, undue focus on single instead of joint biomarker signatures, and incomplete accounting for potential confounding factors. Future multivariable and multi-level approaches may be best suited to find valid candidate biomarkers, which will then need to be validated in external, independent samples and then, importantly, tested in terms of feasibility and cost-effectiveness, before they can be implemented in daily clinical practice. 相似文献
145.
Forbes SH; Hogg JT; Buchanan FC; Crawford AM; Allendorf FW 《Molecular biology and evolution》1995,12(6):1106-1113
We compared genotypes at eight (AC)n microsatellite loci in domestic sheep
(Ovis aries) and wild Rocky Mountain bighorn sheep (O. canadensis). The
domestic sheep had greater genetic variation, higher allele-size variances,
and larger allele sizes than the wild sheep. Accumulating evidence from
higher taxonomic comparisons shows that these parameters are biased if
microsatellite loci are selected in one taxon and used in another. Our
results demonstrate similar biases between congeneric species. We compared
standard measures of genetic variation, differentiation, and distance
within and between species (H, D, FST) to newer measures based on
allele-size variance (SW, SB, RST). The size-based distances better
detected species-level divergence, but standard measures better
distinguished allopatric populations. Empirical calibration of these
measures at the subspecies level is needed to establish their useful
ranges.
相似文献
146.
Everted rectal sacs of Schistocerca gregaria absorb 14C-acetate from the lumen side at high rates against large electrical and often small concentration differences. Most of the 14C-activity in the absorbed fluid remains as acetate, but small amounts serve as substrate for aerobic respiration within this tissue. When acetate is substituted for SO4?2 or Cl? in external salines, both short-circuit current (Isc) and the open-circuit transepithelial potential (PD) increase by as much as 2- to 3-fold. The stimulatory effect of acetate on Isc and PD exhibits saturation kinetics. The ‘steady-state’ influx of 14C-acetate from lumen (L) to haemocoel (H) side greatly exceeds efflux (haemocoel to lumen) across short-circuited recta. Over the whole range of acetate concentrations tested, the resulting net flux of acetate is sufficient to explain all of the increase in Isc caused by this organic anion. Acetate was detected in moderate concentrations in body fluids of locusts. The possible significance of acetate transport in vivo is discussed. 相似文献
147.
The distribution of flourescently labeled α-actinin after microinjection into fibroblasts has been determined in both living and fixed cells. We have found that the distribution of the injected tetramethylrhodamine isthiocyanate-labeled protein (TMRITC-α-actinin) in living cells, which is in ruffling membranes, actin microfilament bundles, and polygonal microfilament networks (Feramisco, 1979, Proc. Natl. Acad. Sci. U. S. A. 76:3967-3971), was virtually unaffected by the fixation (3.5 percent formaldehyde) and extraction (absolute acetone) used for the preparation of the cells for immunoflourescence. Also, these patterns were found to coincide with the α-actinin revealed by immunoflourescence. Also, these patterns were found to coincide with the α-actinin revealed by immunoflourescence. These findings offer, for the first time, evidence indicating the validity of the immunoflourescence technique in the localization of α-actinin in cultured cells. With the combination of the injection procedure and the immunoflourescence localization of endogenous structural proteins, it was determined that nearly all of the actin stress fibers were decorated in a periodic manner with the injected α-actinin. Endogenous tropomyosin in the injected cells was found to be distributed with a periodic pattern along the stress fibers that was antiperiodic to the pattern observed for the microinjected α-actinin. The tropomyosin antibody stained the polygonal microfilament networks and was excluded from the foci, whereas the microinjected α-actinin was incorporated into the foci of the networks. Thus, the microinjected fluorescent derivative of α-actinin appears to be incorporated into the functional pools of α-actinin within the living cell and to be utilized by the cell with fidelity. 相似文献
148.
J Peters S Rudolf H Oschkinat R Mengele M Sumper J Kellermann F Lottspeich W Baumeister 《Biological chemistry Hoppe-Seyler》1992,373(4):171-176
The S-layer protein of Acetogenium kivui was subjected to proteolysis with different proteases and several high molecular mass glycosaminoglycan peptides containing glucose, galactosamine and an unidentified sugar-related component were separated by molecular sieve chromatography and reversed-phase HPLC and subjected to N-terminal sequence analysis. By methylation analysis glucose was found to be uniformly 1,6-linked, whereas galactosamine was exclusively 1,4-linked. Hydrazinolysis and subsequent amino-acid analysis as well as two-dimensional NMR spectroscopy were used to demonstrate that in these peptides carbohydrate was covalently linked to tyrosine. As all of the four Tyr-glycosylation sites were found to be preceded by valine, a new recognition sequence for glycosylation is suggested. 相似文献
149.
The degradation of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) by insulin-degrading enzyme (IDE) has been investigated. As revealed by high-performance liquid chromatography, all three peptides are sequentially cleaved at a limited number of sites, the latter of which were identified by mass spectrometric analyses. The studies revealed that ANP is preferred as substrate over BNP and CNP. ANP degradation is rapidly initiated by hydrolysis at the Ser25-Phe26 bond. Three additional cleavage sites were identified in ANP after prolonged incubation with IDE; in contrast, three and two bonds were hydrolyzed in BNP and CNP, respectively. Analysis of the nine cleavage sites shows a preference for basic or hydrophobic amino acid residues on the carboxyl side of a cleaved peptide bond. In contrast to most of the peptide fragments generated by IDE activity, the initial ANP cleavage product, F-R-Y, is rapidly degraded further by cleavage of the R-Y bond. Cross-linking studies with 125I-ANP in the presence of sulfhydryl-modifying agent indicate that IDE activity is inhibited at the level of initial substrate binding whereas metal-ion chelating agents only prevent hydrolysis. On the basis of its structural and enzymatic properties, IDE exhibits striking similarity to a number of recently-described endopeptidases. 相似文献
150.
Chaperonin-mediated protein folding: GroES binds to one end of the GroEL cylinder, which accommodates the protein substrate within its central cavity. 总被引:18,自引:1,他引:17
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The mechanism of GroEL (chaperonin)-mediated protein folding is only partially understood. We have analysed structural and functional properties of the interaction between GroEL and the co-chaperonin GroES. The stoichiometry of the GroEL 14mer and the GroES 7mer in the functional holo-chaperonin is 1:1. GroES protects half of the GroEL subunits from proteolytic truncation of the approximately 50 C-terminal residues. Removal of this region results in an inhibition of the GroEL ATPase, mimicking the effect of GroES on full-length GroEL. Image analysis of electron micrographs revealed that GroES binding triggers conspicuous conformational changes both in the GroES adjacent end and at the opposite end of the GroEL cylinder. This apparently prohibits the association of a second GroES oligomer. Addition of denatured polypeptide leads to the appearance of irregularly shaped, stain-excluding masses within the GroEL double-ring, which are larger with bound alcohol oxidase (75 kDa) than with rhodanese (35 kDa). We conclude that the functional complex of GroEL and GroES is characterized by asymmetrical binding of GroES to one end of the GroEL cylinder and suggest that binding of the substrate protein occurs within the central cavity of GroEL. 相似文献